DESCRIPTION (adapted from application abstract): Understanding the molecular events that occur after P. falciparum sporozoites infect hepatocytes and develop into fully mature liver stage schizonts and beyond is critical if a rational approach towards identifying candidate molecules for vaccines or for drug design is to be followed. One of the limiting barriers to the study of the hepatic stages is the lack of suitable material for analysis. Primary human hepatocytes which can support the complete development of the parasite can be infected with viable sporozoites at a variable rate between 1 in 10,000 and 1 in 100,000 cells being infected. This variable low level of infection hinders subsequent analysis. If the rate of parasite uptake could be increased by several orders of magnitude to 1 in 100 or higher, and parasite development demonstrated, the subsequent task of following developmentally regulate parasite gene expression may be greatly facilitated. Here the application proposes to investigate an approach to provide an alternative parasite recognition and internalization pathway to enhance parasite recognition and uptake by engineered cell lines to permit subsequent development to be examined. The thrust of this application is to investigate the de novo design of artificial cell receptors for pathogen uptake.